One important step in neuromuscular transmission is the combination of acetylcholine (Ach) released from motor nerve terminals, with a specific protein receptor in the muscle membrane. The interaction of ACh with the receptor causes an increase in sodium and potassium permeabilities of the membrane, resulting in depolarization and eventually contraction of the muscle. Normally the ACh receptor in vertebrate skeletal muscle occurs almost exclusively in the muscle membrane underlying the nerve terminal. When a muscle is denervated, however, ACh receptors also appear in the muscle membrane that is not associated with the neuromuscular junction, so that the entire muscle surface is sensitive to ACh. After reinnervation of the muscle, the number of ACh receptors in the extrajunctional membrane again diminishes. The functional significances of these changes is not understood, but they may be of developmental significance, since ACh receptors occur over the entire surface of newly-innervated muscles and myotubes formed in culture in the absence of nerves. Our research has focused on the biochemical properties of the ACh receptors in muscle and the mechanisms that control their concentration. We are using a small radioactive protein, 125I-alpha-bungarotoxin, that binds tightly and specifically to the receptor in our studies. The toxin allows us to assay the receptor after extraction from the muscle and thus to purify it for further study. In addition, toxic bound to the receptor in situ is useful for studies of the dynamic properties of the receptor in the membrane.